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<p>Cancer of unknown primary (CUP), a&#xa0;rare metastatic malignancy for which a&#xa0;primary site cannot be established after the diagnostic workup, has an unfavorable prognosis. Histopathological assessment, including comprehensive panels of immunohistochemistry (IHC) of biopsy specimens, remains the mainstay for establishing a&#xa0;diagnosis, identifying a&#xa0;putative tissue of origin (ToO), and guiding therapy decisions. Combining IHC and complex molecular analyses may identify therapy targets to improve patient outcomes. This review focuses on the standard-of-care diagnostic workup of suspected CUP samples, the pathologist’s role in the search for therapy targets, and current as well as future developments in the field.</p>

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Diagnostic approaches to cancer of unknown primary—the pathologist’s perspective

  • 期刊论文

  • 发表日期：

    2025年12月17日

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  • Michael Guenther,
  • Andrea Brunner-Véber,
  • Steffen Ormanns

摘要

Cancer of unknown primary (CUP), a rare metastatic malignancy for which a primary site cannot be established after the diagnostic workup, has an unfavorable prognosis. Histopathological assessment, including comprehensive panels of immunohistochemistry (IHC) of biopsy specimens, remains the mainstay for establishing a diagnosis, identifying a putative tissue of origin (ToO), and guiding therapy decisions. Combining IHC and complex molecular analyses may identify therapy targets to improve patient outcomes. This review focuses on the standard-of-care diagnostic workup of suspected CUP samples, the pathologist’s role in the search for therapy targets, and current as well as future developments in the field.